Fluoroalkenyl compounds and their use as pest control agents

ABSTRACT

Novel 3,4,4-trifluorobutenoic acid derivatives of the formula &lt;IMAGE&gt;  wherein Q is -(C=W)-R2 wherein W is O or S, and R2 is an aliphatic or aromatic group when W=O; -OR50; -SR50; or -NR50R60 wherein R60 is hydrogen or R50; NR7R8; a heterocyclic group; phenyl substituted by alkyl; or any agronomically acceptable salt thereof having usefulness as nematocides, insecticides and acaricides.

This application is a Divisional of U.S. Ser. No. 08/329,593 filed Oct.26, 1994, now U.S. Pat. No. 5,514,717.

FIELD OF THE INVENTION

The present invention relates to certain fluoroalkenyl compounds, theirderivatives and salts, and formulated compositions thereof. It alsorelates to methods of controlling pests that prey on agricultural crops,such as nematodes, insects, and acarids. New and efficient methods toprepare 3,4,4-trifiuoro-3-butenoic acid, a key intermediate, are alsoprovided.

BACKGROUND OF THE INVENTION

Fluorinated alkenes have long been known to control nematodes andinsects when applied to the soil. U.S. Pat. Nos. 3,510,503, 3,654,333,and 3,780,050 all disclose such compounds. More recently, U.S. Pat. No.4,952,580 disclosed polyhaloalkenes useful as nematocides, some of whichwere said to have some downward systemic activity, that is, wouldcontrol to some extent nematode infestation of the root system afterapplication to the plant foliage. The majority of the compoundsdisclosed by these patents are nonpolar, which is a desirablecharacteristic for soil-applied pesticides, providing longer effectiveperiods, but is much less effective for foliar application to achievesystemic effects. U.S. Pat. No. 4,950,666 discloses some polardifiuoro-alkenylalkane compounds useful as systemic insecticides andnematocides. PCT Publication Number WO 92/15555 discloses fluoroalkenylcompounds, including mono-, di- and trifluoroalkenylamines andtrifiuoroalkenyl-carboxylic acids for controlling pests such asnematodes, insects and acarids. However, there remains a need in the artfor nematode, insect, and acarid control agents having improved systemicmobility, and desirably with low effective levels of use.

SUMMARY OF THE INVENTION

The present invention provides compounds, useful for controllingnematode, insect, and acarld infestation of a plant, having thestructure (I): ##STR2## wherein Q is --(C═S)--R₁, --(C═W)--R₂ or--(P═W)R₃ R₄ ; wherein

W is O or S;

R₁ is --OR₅, --SR₅ , halogen, --NHOH, or --NR₅ R₆ ; wherein each of R₅and R₆ is independently

(i) hydrogen;

(ii) an aliphatic or an aromatic group, optionally substituted with atleast one group selected from hydroxy, alkoxy, halo, nitro, amino,thiol, alkylthio, carboxyl, alkoxycarbonyl, and phenyl;

(iii) a C₁ -C₁₂ aliphatic amine group, optionally substituted with atleast one group selected from hydroxy, alkoxy, halo, nitro, amino,thiol, alkylthio, carboxyl, alkoxycarbonyl, and phenyl;

(iv) a C₂ -C₁₂ aliphatic carboxylic acid group, optionally substitutedwith at least one group selected from hydroxy, alkoxy, halo, nitro,amino, thiol, alkylthio, carboxyl, alkoxycarbonyl, and phenyl; or

(v) R₅ and R₆ taken together with the N of R₁ are a protein acid or acyclic group selected from a radical of morpholine, piperidine,piperazine, or pyrrolidine, optionally substituted with at least onegroup selected from hydroxy, alkoxy, halo, nitro, amino, thiol,alkylthio, carboxyl, alkoxycarbonyl, and phenyl;

R₂ is (a) an aliphatic or aromatic group, provided that W═O, each ofwhich is optionally substituted with at least one group selected from aradical of sulfonic add, phosphonic acid, phosphinic acid, carboxylicacid, their esters, amides and thiol esters, cyano, trimethylsilyl,hydroxy, alkyl, alkoxy, halo, nitro, amino, thiol, alkylthio, andphenyl;

(b) OR₅₀ ^(--SR) ₅₀, or NR₅₀ R₆₀

wherein R₆₀ (i) hydrogen, R₅₀

wherein R₅₀ (ii) an aliphatic, an aromatic, or a heterocyclic group,substituted with at least one group selected from a radical of sulfonicadd, phosphonic add, phosphinic add, their esters, amides and thiolesters, cyano, trimethylsilyl and optionally further substituted withone of hydroxy, alkoxy, halo, nitro, amino thiol, alkylthio, carboxyl,alkoxycarbonyl, or phenyl;

(iii) a C₁ -C₁₂ aliphatic amine group substituted with at least onegroup selected from a radical of sulfonic acid, phosphortic add,phosphinic acid, their esters, amides and thio esters, cyano,trimethylsilyl and optionally further substituted with one of hydroxy,alkoxy, halo, nitro, amino, thiol, alkylthio, carboxyl, alkoxycarbonyl,or phenyl;

(iv) a C₂ -C₁₂ aliphatic carboxylic acid group, esters, amides and thioesters thereof, substituted with at least one group selected from aradical of sulfonic acid, phosphonic acid, phosphinic acid, theiresters, oraldes and thiol esters, cyano, trimethylsilyl and optionallyfurther substituted with one of hydroxy, alkoxy, halo, nitro, amino,thiol, alkylthio, carboxyl, alkoxycarbonyl, or phenyl;

(v) R₅₀ and R₆₀ taken together with the N of R₂ are a protein amino acidor a cyclic group selected from a radical of morpholine, piperidine,piperazine, or pyrrolidine, substituted with at least one group selectedfrom a radical of sulfonic acid, phosphonic acid, phosphinic acid, theiresters, amides and thio esters, cyano, trimethylsilyl and optionallyfurther substituted with one of hydroxy, alkoxy, halo, nitro, amino,thiol, alkylthio, carboxyl, alkoxycarbonyl, or phenyl;

(vi) R₅ and R₆ taken together with the N of R₂ are pyrazole, imidazoleor triazole, optionally substituted with at least one group selectedfrom a radical of sulfonic acid, phosphonic acid, phosphinic acid,carboxylic acid, their esters, amides and thio esters, cyano,trimethylsilyl, hydroxy, alkoxy, halo, nitro, amino, thiol, alkylthio,or phenyl;

(vii) a heterocyclic group optionally substituted with at least onegroup selected from a radical of sulfonic acid, phosphonic acid,phosphinic acid, carboxylic acid, their esters, amides and thio esters,cyano, trimethylsilyl, hydroxy, alkoxy, halo, nitro, amino, thio,alkylthio, or phenyl;

(viii) phenyl substituted by alkyl and optionally further substituted bya radical of sulfonic acid, phosphonic acid, phosphinic acid, carboxylicacid, their esters, amides and thio esters, cyano, trimethylsilyl,hydroxy, alkoxy, halo, nitro, amino, thiol, alkylthio, or phenyl;

(c) NR₇ R₈ ; wherein R₇ is hydrogen, aliphatic or an aromatic group eachof which is optionally substituted with at least one of the group ofhydroxy, alkoxy, halo, nitro, amino, thiol, alkylthio, carboxyl esters,carboxyl amides, carboxyl thioesters or phenyl; R₈ is independentlyphenyl or substituted phenyl, --OR₉, --C(O)R₉, --NR₉ R₁₀, --S(O)₂ R₁₁,--P(═O)R₁₂ R₁₃ where R₉ and R₁₀ are independently H, alkyl or aryl, R₁₁is hydrogen, alkyl, haloalkyl or aryl, R₁₂ and R₁₃ are independently H,alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, alkylamino,dialkylamino, arylamino, --OR₁₄ wherein R₁₄ is H, alkyl or aryl;

(d) a heterocyclic group optionally substituted with a radical ofsulfonic acid, phosphortic acid, phosphinic acid, carboxylic acid, theiresters, amides and thioesters, cyano, trimethylsilyl, hydroxy, alkoxy,halo, nitro, amino, thiol, alkylthio, or phenyl; with the proviso thatwhen W═S, then the point of attachment to the heterocyclic group must bethrough a N atom;

(e) phenyl substituted by alkyl and optionally further substituted by aradical of sulfonic acid, phosphonic acid, phosphinic acid, carboxylicacid, their esters, amides and thioesters, cyano, trimethylsilyl,hydroxy, alkoxy, halo, nitro, amino, thiol, alkylthio, or phenyl,provided that W═O;

R₃ and R₄ are independently R₁₅, --OR₁₅, --SR₁₅, --NR₁₅ R₁₆ where R₁₅and R₁₆ are independently selected from the group consisting ofhydrogen; an aliphatic or an aromatic group, optionally substituted withat least one group selected from a radical of sulfonic acid, phosphonicacid, phosphinic acid, carboxylic acid, their esters, amides and thiolesters, cyano, trimethylsilyl, hydroxy, alkoxy, halo, nitro, amino,thiol, alkylthio, phenyl;

or an agronomically acceptable salt thereof.

This invention also includes methods to prepare3,4,4-trifiuoro-3-butenoic acid (IV), a key intermediate for thepreparation of the compounds of the present invention. These methods arecost effective and/or use intermediates which are not known in thegeneral literature. These methods include:

Refer to Scheme 1

(1a) Hydrolysis of4-bromo-1,1,2-trifiuoro-1-butene (II) with water inN-methylpyrrolidinone to give 3,4,4-trifluoro-3-buten-1-ol (III);

(1b) Jones oxidation of III under specific conditions to give3,4,4-trifiuoro-3-butenoic acid (IV) in 52% overall yield; or

Refer to Scheme 2

(2a) A one pot reaction of 1-chloro-1,2-dibromotrifluoroethane (VI) withethyl vinyl ether in the presence of sodium hydrosulfite/sodiumbicarbonate followed by oxidation of the intermediate,4-bromo-3-chloro-3,4,4-trifluorobutanal (VII), without isolaton, withsodium chlorite/hydrogen peroxide to give4-bromo-3-chloro-3,4,4-trifiuorobutanoic acid (VIII) in overallunexpected yields;

(2b) Alternatively, the intermediate VII can be reduced with sodiumborohydride without isolation to give4-bromo-3-chloro-3,4,4-trifiuorobutanol ((IX) in high yield; or byhydrolysis of 1,4-dibromo-2-chloro-1,1,2-trifiuorobutane (XVI) to giveIX. Oxidation of IX with Jones reagent to give VIII in 85% yield.

(2c) Dehalogenation of 4-bromo-3-chloro-3,4,4-trifluorobutanoic acid(VIII) with zinc using conditions analogous to those disclosed in theliterature to obtain the desired 3,4,4-trifluoro-3-butenoic acid (IV);or

Refer to Scheme 3

(3a) A one pot reaction of 1-chloro-1,2-dibromotrifluoroethane (VI) or1,1,2-trichlorotrifiuoroethane (X) with vinylidene chloride in thepresence of ammoninm persulfate/sodium formate/air in DMF to give4-bromo-3-chloro-3,4,4-trifiuorobutanoic acid (VIII) or 3,4-dichloro-3,4,4-trifluorobutanoic acid (XI).

(3b) Dehalogenation of VIII or XI with zinc to give3,4,4-trifiuoro-3-butenoic acid (IV).

This invention also includes methods to prepare a compound of theformula I where Q═--(C═O)R₂, which comprises:

Refer to Scheme 1

(4a) Reaction of 3,4,4-trifiuoro-3-butenoic acid (IV) with oxalylchloride in the presence of DMF as a catalyst without any solvent togive 3,4,4-trifluoro-3-butenoyl chloride (V).

(4b) Reaction of V with an appropriate reagent in aqueous oraqueous/-organic solvent medium in the presence of an acid scavangersuch as sodium bicarbonate to give a compound of the fomula XVII.

Refer to Scheme 4

(5a) Conversion of VIII to 4-bromo-3-chloro-3,4,4-trifiuorobutanoylchloride (XII) by reacting with appropriate reagents known in theliterature, for example, oxalyl chloride.

(5b) Reaction of XII with appropriate reagents in aqueous oraqueous/-organic solvent medium in the presence of an acid scarangersuch as sodium bicarbonate to give novel compounds XIII, for example,XIV.

(5c) Dehalogenation of XIII with zinc to give compounds of the formulaXVII.

(6) The above steps 5a, 5b, or 5c can also be carried out with XI inplace of VIII to prepare the compounds of the formula I whereQ═--(C═O)R₂.

The steps 4b, 5a, 5b, 5c, and 6 (above) are also useful to preparecompounds of the formula F₂ C═CF--CH₂ --(C═O)--R₂ as disclosed in WO92/15555 which is incorporated herein by reference.

The compounds IX, XI, XII, and XIV are novel intermediates.

Compounds of the present invention also include, Where possible,hydrated species. Those skilled in the art will recognize that alternatesubstituents may be identified that will provide substantiallyequivalent results.

Preferred compounds of this invention are of the formula (I): ##STR3##wherein Q is (C═S)--R₁ or (C═W)--R₂ ; wherein W is 0 or S; and R₁ and R₂are as described above. Most preferred compounds are where (C═O)R₂ andR₂ is NR₇ R₈ where R₇ is H and R₈ is --S(O)₂ R₁₁, where R₁₁ is alkyl orhaloalkyl and their agronomically acceptable salts.

The present invention includes compositions for controlling nematodeinfestation of a plant comprising an effective amount of a compound offormula I, or an agronomlcally acceptable salt thereof, in anagronomically acceptable carrier.

The present invention includes a method of systemically controllingnematode, insect or acarid infestation of a plant, comprising applyingto a plant locus an effective amount of a formula I or an agronomicallyacceptable salt thereof.

DETAILED DESCRIPTION OF THE INVENTION

The novel compounds of the present invention are useful for controllingnematode, insect, and acarid infestation of a plant. Many of thesecompounds, being polar, are highly effective for systemic control, thatis, when applied to the foliage or stems of a plant they are able tomove through the phloem and xylem of the plant and provide control ofnematodes, insects, or acarids at other locations on the plant. It isbelieved that this control mechanism is a repelling or antifeedantaction, rather than a harming action. Others, particularly the nonpolarcompounds, are effective only when applied directly to the soil. Somecompounds can provide both types of control.

The present methods for systemic control of nematodes, insects, andacarids use the phloem mobile compounds of the present invention orthose compounds having sufficient polarity to allow for phloem-mobilitywithout eliminating the nematode-controlling activity of thefluoroalkene moiety. There are several different theories concerningphloem mobility, such as what polarity characteristics compounds musthave to be sufficiently phloem mobile in order to be relocated downwardin a plant. It has been proposed that the polarity of the molecule as awhole must be sufficient for the molecule to be retained in the phloem,but not be so polar as to not enter at all.

To effectively control nematodes or other posts systemically byapplication to the above-ground surfaces of a plant, compounds must becapable of passing through the cuticle of the foliage or stem of aplant, passing into the phloem, and remaining there long enough to betransported throughout the plant so as to move to untreated areasincluding the roots. There they may leak out or in some way contact thepests to such an extent that they are killed or repelled and the damagethey would do to the plant is reduced or eliminated. During these stepsof transport from the treated areas of leaves or sterns throughout theplant, a compound may undergo chemical reactions, such as hydrolysis, orbiological reactions, such as enzymatic reactions. In addition,compounds may be devised which, when placed on the plant, prior toabsorption into the plant, may undergo reactions that result in acompound that is readily absorbable, translocatable, and effective inpreventing pest damage. An example of such compounds are those havingUV-labile protecting groups which when exposed to natural light undergoreaction and result in active and mobile compounds. Another example issilylated amine derivatives.

Therefore, what is placed on the foliage or stem of the plant may not bethe compound that is actually transported or the compound that actuallycontrols the pests. Thus, the methods of the present invention providefor compounds that may be transformed through chemical or biologicalreactions to have proper polarity for systemic activity.

The methods of the present invention include applying compounds of thepresent invention to the plant locus, preferably to the foliage. Thecompounds can also be applied to the soil or as seed treatments. Alsoincluded are compositions comprislngan aqueous solution of the activeingredient in an agronomically acceptable carrier.

In addition to the compounds specifically described above, allagronomically acceptable salts of the compounds are within the scope ofthe present invention. A compound of the present invention having acarboxylic acid or hydroxyl group may exist as the salt having variouscations associated therewith, for example, but not limited to, alkaliearth metals, such as sodium, calcium, and potassium; magnesium; orquaternary ammonium ions, such as ammonium, mono-, di-, ortrialkylammonium, for example, isopropylammonium, or pyridinium.

As used herein, the term "halo", "halide", or "halogen" means fluorine,chlorine, iodine, or bromine or cognates thereof.

The term "alkyl" means straight-chain or branched groups of from one toabout seven carbon atoms.

The term "lower alkyl" means a group containing from one to about fourcarbon atoms.

The term "aliphatic" means saturated or unsaturated, branched orstraight-chain, alkyl groups having from one to about ten carbon atoms.

The term "alkoxy" means a lower alkyl group bonded via an oxygen atom.

The term "alkylthio" means a lower alkyl group bonded via a sulfur atom.The term "alkoxycarbonyl" means the lower alkyl ester of a carboxylgroup.

The term "aliphatic amino" means an aliphatic group wherein at least onehydrogen is replaced with --NH₂.

The term "aliphatic carboxylic acid, amides, esters, and thio esters"means an aliphatic group wherein at least one carbon is a carboxylicgroup, --COOH, or is the lower alkyl ester, amide, or lower alkyl thioester, thereof.

As used herein, the phrase "amino acid amide of Q" means that R₆ is anamino acid coupled via a peptide (amide) bond to the C═O of Q. Thisamino acid may be a natural, i.e., protein, amino acid or a nonnaturallyoccurring amino acid. The amino group of the amino acid may be asubstituent of any carbon in the group, for example, alpha, beta, orgamma to the carbonyl.

The term "alkyl or aryl sulfonamide" means a sulfonamide groupsubstituted with a lower alkyl or phenyl group, which in turn may beoptionally substituted.

The term "aromatic group" or "aryl" means phenyl, optionally substitutedwith at least one group selected from hydroxy, alkyl, alkoxy, halo,nitro, amino, thiol, alkylthio, carboxyl, alkoxycarbonyl, and phenyl.

The term "heterocyclic" means any cyclic compound which contains atleast one other element other than carbon as a member of the ring. Thering may be saturated or unsaturated. The hetero atom may be oxygen,nitrogen, sulfur, or some other element. Heterocycles include, forexample, thiadiazole, pyridine, thiazole, isothiazole, oxazole,imidazole, pyrazole, triazole, benzothiazoie, thiophene, furan, and thelike, all of which may also be optionally substituted. The carbon atomsof the heterocyclic rings optionally may be substituted with any groupor groups which are non-destructive of the nematocidal activity of thecompounds. Typical substituents include aliphatic, aromatic andheterocyclic groups, halo, nitro, cyano, alkoxy, alkylthio, haloalkyl,haloalkoxy, halo-, nitro-, cyano- or alkoxy-substituted phenyl,polyhaloalkenylthio, phenylalkylthio, phenylthioalkylthio,propargylthio, cycloalkylmethylthio and the like, further includingstraight and branched chain structures, and the various isomers of suchsubstituents.

COMPOUND SYNTHESIS

Most of the compounds of the present invention are prepared by reacting3,4,4-trifluoro-3-butenoyl chloride (V) with appropriate reagent inaqueous or aqueous/organic solvent medium in the presence of an acidscavenger such as sodium bicarbonate.

Synthesis of 3,4,4-trifluoro-3-butenoic acid Method 1, Scheme 1,Compound IV

The first method involves hydrolysis of 4-bromo-1,1,2-trifluoro-1-butene(II) with water in the presence of N-methyl pyrrolidinone to give3,4,4-trifiuoro-3-buten-1-ol (III), followed by Jones oxidation underconditions not previously known. These conditions are at a temperatureof about 51°-54° C. In addition, the 3,4,4-trifluoro-3-buten-1-ol inacetone solvent and the Jones reagent are added to the reaction vesselsimultaneously to afford 3,4,4-trifluoro-3-butenoic (IV) acid in 52%overall yield. ##STR4##

Method 2, Scheme 1, Compound IV

In the second method the synthesis of4-bromo-3-chloro-3,4,4-trifiuoro-butanoic acid (VIII) is followed byzinc dehalogenation to produce 3,4,4-trifiuoro-3-butenoic acid (IV).This compound is prepared by reacting1-chloro-1,2-dibromotrifiuoroethane (VI) with ethyl vinyl ether in thepresence of sodium dithionite and sodium bicarbonate in a manneranalogous to that described in the Literature Huang, Weiyuan; lu, long;Zhang, Yuanfa; Chin. J. Chem. 1990, (3), 281!. However, it is now foundthat the 4-bromo-3-chloro-3,4,4-trifluorobutanal intermediate (VII) isoxidized without isolation with sodium chlorite/hydrogen peroxide. Inother words, instead of oxidation with Jones reagent, this methodadvantageously provides a process which can be carried out in onereaction vessel using preferred reagents and gives an unexpectedly highyield.

Oxidation of VII is also carried out by following reaction conditionssimilar to those described in Dalconale, D. and Montanari, F; J. Org.Chem., 1986, (51) 567. Alternative oxidation conditions are analogous tothose described in the Literature Huang, Weiyuan; Lu, Long; Zhang,Yuanfa; Chin. J. Chem., 1990, (3), 281; Nwauka, et al., TetrahedronLetters. 1982, 3131; and Yamada, T., et al., Chemistry Letters. 1991,5!. In other words, 4-bromo-3-chloro-3,4,4-trifluorobutanal intermediatecan be oxidized to 4-bromo-3-chloro-3,4,4-trifiuorobutanoic acid byusing various other oxidizing conditions known in the generalliterature.

Alternatively, the aldehyde intermediate VII can be reduced with sodiumborohydride to give the novel compound which is a corresponding alcoholIX in excellent yield. In addition, the alcohol intermediate (IX) can beprepared by hydrolysis of XVI. Jones oxidation of IX gave VIII in 85%yield. Dehalogenation of VIII with zinc in water gave the desired3,4,4-trifiuoro-3-butenoic acid (IV) in 85% yield. ##STR5##

Method 3, Scheme 3, Compound IV

A new method to prepare the desired 3,4,4-trifluoro-3-butenoic acid (IV)involves a one pot reaction of 1-chloro-1,2-dibromotrifluoroethane (VI)or 1,1,2-trichloretrifluoroethane (X) with vinylidene chloride in thepresence of ammonium persulfate/sodinm formate/air in DMF to givedirectly 4-bromo-3-chloro-3,4,4-trifluorobutanoic acid (VIII) or novelcompound 3,4-dichloro-3,4,4-trifiuoro-butanoic acid (XI). The reactionconditions to prepare XI from X are similiar to those described in Hu,Chang-Ming; Qing, Feng-Ling, Zhang, Hong-Gen; J. Fluorine Chem., 1990,(49) 275-280. The formation of XI in the above reaction was confirmed byGC/MS (EI): m/z 212 CM++2), 210 (M+), 195, 193, 157, 155, 127,125,107,105, 89, 69, 45. Dehalogenation of VIII or XI with zinc gives IV.##STR6## he compounds of formula XVII can also be prepared by analternate method to prepare selected compounds of formula I asexemplified with XV shown in Scheme 4. The reaction sequence shown inScheme 4 using novel intermediates XII and XIII exemplified by XIV canalso be carried out by substituting XI in place of VIII to preparecompounds of formula XVII. ##STR7##

Synthesis of 3,4,4-trifluoro-3-butenoic acid Method 1,Scheme 1, CompoundIV

A mixture of 4-bromo-1,1,2-trifiuoro-1-butene (II) (3.0 kg, 16.67 mol)water (1.51 L, 83.9 mol) and N-methylpyrrolidinone (9.06 L) in a 22 L4-necked round-bottom flask was heated at reflux under nitrogen for 20h. Water (4.53 L) was added and the solution was distilled through a 50cm Vigreux column in tandem with a Dean-Stark trap to maintain aconstant water volume in the pot. The lower layer in the trap (azeotropebp 96°-100.6° C.) was drawn off periodically as the distillationprogressed to give 3,4,4-trifluoro-3-buten-1-ol (III) (1706 g, 81.2%) asa clear liquid, which is used directly in the next step.

A mechanically stirred 12 L glass reactor clad with a jacket cooled withtap water was charged with 100 mL of acetone and 100 mL of Jonesreagent. A solution of 3,4,4-trifiuoro-3-buten-1-ol (850 g, 6.75 mol)diluted to a total volume of 5.0 L in acetone was added simultaneouslywith 5.0 L of Jones reagent via a twin head peristaltic pump capable ofof a pump rate ca. 120 mL/min. A reaction temperature of 51°-54° C. wasmaintained by adjusting the pnmp rate and the tap water cooling flow.Following the addition (45 min), the mixture was allowed to cool to35°-40° C. over 30-60 min. The reaction mixture was transferred to aseparatory funnel and layers separated. The upper layer was washed oncewith brine and concentrated. The lower layer was diluted with water (500mL) and extracted with dichloromethane (3 L). The dichloromethaneextract was combined with the above residue, washed with brine and driedover magnesinm sulfate. Evaporation of the solvent gave 613 g (65%) ofthe desired product as a green oil.

Method 2, Scheme 2, Compound IV

A one L. 3-necked flask equipped with a mechanical stirrer was chargedwith sodium bicarbonate (15.2 g, 181 mmole), potassium dihydrogenphosphate (8.2 g, 60.3 mmol), sodium hydrosulfite (3.15 g, 18.1 mmol)and water (100 mL). After the solids were dissolved, acetonitrile (200mL) was added and the mixture was cooled to 5°-10° C. A mixture of1,2-dibromo-1-chlorotrifluoroethane (VI) (50 g, 181 mmol) and ethylvinyl ether (18.1 g, 250 mmol, 24 mL,) was taken in a dropping funnel,and approx. 20% was added rapidly with stirring. After one or twominutes, a slight exotherm (2 or 3 degrees raise in temperature)occurred. Following that, addition was continued while keeping theinternal temperature at 10°-15° C. After the addition was complete (10min), the mixture was stirred for another 15 min at 10°-15° C. GCanalysis of an aliquot in ether indicated completion of the reaction.

The above mixture was cooled to 5 ° C. and 30% hydrogen peroxide (23.59g, 208 mmol) was added first two or three mL dropwise (exotherm) and theremaining in one portion. A solution of sodium chlorite (80% assay, 23.1g, 204 mmol) in 75 mL of water was added dropwise with stirring whilekeeping the internal temperature 10°-15° C. (exothermic reaction). Theaddition took approx. 30 min. After the addition was complete, themixture was stirred at 15° C. for 30 min and at room temperature foranother 60 min. GC analysis of an aliquot indicated the reaction wasessentially complete. The mixture was cooled to ca. 10 ° C. and sodiumsulfite (7.5 g) was added in portions with stirring. After 10 min ofstirring, peroxide test (starch iodide paper) indicated negative. Themixture was treated with 20 mL of 6N HCl and transferred to a separatoryfunnel. The top organic layer was separated and concentrated on a rotaryevaporator to a weight of 58.7 g.

The above crude bromochlorotrifluorobutanoic acid (58.7 g) was treatedwith 50 mL of water and cooled in ice-water bath. Zinc dust (15.0 g,0.230 gatom) was added in portions with stirring. The reaction is veryexothermic but does not hurt the formation of the desired product; infact it accelerates the reaction. After the addition was complete (20min), the mixture was stirred at room temperature until exothermsubsided (another 20 min). The mixture was transferred to a separatoryfunnel by pouring through a plug of glass wool (to remove chunks of zincsalts), diluted with 6N HCl (ca. 25 and extracted with dichloromethane(2×100 mL). The dichloromethane extract (top layer) was washed with 6NHCl (30 min) and brine (100 mL) and dried over anhyd. MgSO₄. Evaporationof the solvent gave 19.28 g (76% for the two steps) of the crude3,4,4-trifluoro-3-butenoic acid (IV) as a pale yellow liquid.

Synthesis of 3,4-dichloro-3,4,4-trifluorobutanoic acid Scheme 3,Compound XI

A mixture of 1,1,2-trichlorotrifluoroethane (X) (9.37 g, 50 mmol),vinylidene chloride (4.85 g, 50 mmol), ammonium persulfate (11.41 g, 50mmol), sodium formate (3.4 g, 50 mmol) and water (1.8 g, 0.1 mol) in DMF(80 mL) was stirred (dry-ice/acetone condensor) at room temperature withair bubbling. After 30 min, an aliquot of the reaction mixture wasacidified with dilute HCl, extracted with ether and analyzed by GC,which indicated the formation of two products. These products wereidentified by GC/MS (EI) as 4-chloro-3,4,4-trifluoro-2-butenoic acid andnovel compound 3,4-dichloro-3,4,4-trifluorobutanoic acid (XI). Thecompound XI gives 3,4,4-trifluoro-3-butenoic acid (IV) upon reactionwith zinc. Under the above reaction conditions,1-chloro-1,2-dibromotrifluoroethane (VI) gave3-chloro-4-bromo-3,4,4-trifluorobutanoic acid (VIII) as one of theproducts.

Synthesis of 4-bromo-3-chloro-3,4,4-trifluorobutanol Method 1, Scheme 2,Compound IX

A mixture of 1,4-dibromo-2-chloro-1,1,2-trifluorobutane (XVI) (7.5 g,24.6 mmol), 1-methyl-2-pyrrolidinone (14 ml,) and water (2.5 mL) washeated at 130° C. for 16 hours. The mixture was cooled to roomtemperature, diluted with water (80 mL) and extracted with ether (2×75mL). The ether extract was washed with water (3×40 mL), brine, and driedover anhydrous magnesium sulfate. The residue obtained after evaporationof the solvent was chromatographed over silica gel to give 2.9 g (49%)of the desired alcohol as a clear oil.

Method 2, Scheme 2, Compound IX

A solution of sodium hydrosulfite (34.8 g, 0.2 mol) and sodiumbicarbonate (22.0 g, 0.262 mol) in water (400 mL) was treated with 400mL of THF and the mixture was cooled to 5° C. A mixture of1,2-dibromo-1-chlorotrifluoroethane (VI) (55.26 g, 0.2 mol) and ethylvinyl ether (21.6 g, 0.3 mol) was added in one portion to the abovemixture with stirring and cooling. The mixture was then stirred at10°-15° C. for 30 min and then solid sodium chloride was added tosaturate the aqueous layer. The aqueous layer was separated andextracted with THF (100 mL). The combined THF extract was diluted withwater (100 mL) and treated with sodium borohydride (7.57 g, 0.2 mol) inportions with stirring and cooling (ice-water bath). The mixture wasstirred for 30 min and then acidified 3N HCl by dropwise addition. Theaqueous layer was saturated with sodium chloride and the organic layerwas separated, washed with brine and dried over anhydrous magnesiumsulfate. The residue obtained after evaporation of the solvent wasdistilled under vacuum to give 37.7 g (78%) of the desired alcohol as aclear oil, bp 98°-100° C./40 mmHg.

Jones oxidation of 4-bromo-3-chloro-3,4,4-trifluorobutanol Scheme 2,Compound IX

A solution of 4-bromo-3-chloro-3,4,4-trifluorobutanol (IX) (2.41 g, 10mmol) in acetone (35 mL) was treated with Jones reagent (7.5 mL) in 10min with stirring and cooling (ice-water bath). The mixture was thenstirred at room temperature for 30 min and 0.5 mL of i-propanol was thenadded. The precipitated salts were removed by filtration, washed withacetone. The residue obtained after concentration of the flitrate wasdissolved in methylene chloride (100 mL), washed with 1N HCl (50 mL),brine, and dried over anhydrous magnesinm sulfate. Evaporation of thesolvent gave 2.17 g (85%) of 4-bromo-3-chloro-3,4,4-trifluorobutanoicacid (VIII) as a clear oil.

Synthesis of N-(3,4,4-trifluoro-1-oxo-3-butenyl)glycine Scheme 4,Compound XV

A mixture of 4-bromo-3-chloro-3,4,4-trifluorobutanoic acid (8.0 g, 31mmol), oxalyl chloride (5.8 g, 45 mmol) and two drops of DMF inmethylene chloride (40 mL) was stirred at room temperature for 16 hours.The solvent and excess oxalyl chloride were removed by rotaryevaporation to give 8.1 g (95%) of the crude product (XIl) as an yellowliquid.

The above acid chloride (5.7 g, 20.8 mmol) with out any furtherpurification was added to an ice-cold solution of sodium hydroxide (1.6g, 40 mmol), glycine (3.06 g, 40 mmol) in water (15 mL) with stirring.The mixture was stirred in cold for 2.5 hours, acidified with conc. HCl,and extracted with ethyl acetate (2×75 mL). The ethyl acetate extractwas washed with brine and dried over anhydrous magnesium sulfate.Evaporation of the solvent gave 6.33 g (97%) of the crude preduct (XIV)as a yellow gum. Proton NMR spectral analysis of the above crude productindicated the formation of the desired product.

The above crude product (5.77 g, 18.5 mmol) was dissolved in ethanol (15mL), water (10 mL) and treated with zinc dust (1.2 g) in portions withstirring and cooling (tap water). The mixture was then stirred at roomtemperature for 10 min filtered and extracted with ethyl acetate (2×100mL). The ethyl acetate extract was washed with brine and dried overanhydrous magnesium sulfate. Evaporation of the solvent gave a whitesolid, which was triturated with anhydrous ether, filtered and air driedto give 1.65 g (45%) of the desired product (XV).

Synthesis of 3,4,4-Trifluoro-3-butenoyl chloride and Derivatives Scheme1, Compound V

A mixture of 3,4,4- trifluoro-3-butenoic acid (IV) (19.28 g, 138 mmol),oxalyl chloride (21.8 g, 172 mmol; 15 mL) and two drops of DMF wasstirred for 6 hours and distilled at atmospheric pressure undernitrogen. The fraction boiling at 90°-98° C. was collected to give 16.1g (74%) of the desired product as a clear liquid.

The compounds of the present invention are merely illustrated by thefollowing working examples, but are not limited thereto. The examplenumbers which follow correspond to the same example numbers of thestructures and biological data presented below.

EXAMPLE 1 Phosphonic acid, (3,4,4-trifluoro-1-oxo-3butenyl)amino!methyl!-, disodium salt:

A stirred ice-cold mixture of sodium bicarbonate (1.26 g, 15 mmol) anddi-t-butyl aminomethanephosphonate (2.23 g, 10 mmol) in water (20 ml,)and dichloromethane (40 mL) was treated dropwise with3,4,4-trifluoro-3-butenoyl chloride (1.58 g, 10 mmol). After theaddition was complete, the mixture was stirred at room temperature for30 min and the organic layer was washed with brine and dried overanhydrous magnesium sulfate.

Evaporation of the solvent gave 2.98 g (86%) of the desired di-t-butylester, which was dissolved in 15 mL of trifluoroacetic acid and allowedto stand at room temperature for 30 min. The residue obtained afterevaporation of the trifluoroacetic acid was partitioned between ethylacetate (50 mL) and water (25 mL). Concentration of the aqueous layergave 1.5 g of the free acid which was redissolved in water (20 ml,) with1.08 g (12.87 mmol). The solution was concentrated to dryness to give1.98 g of the title compound as a pale yellow solid. mp 190°-200° C.

EXAMPLE 52-(3,4,4-trifluoro-1-oxo-3-butenyl)amino-4,6-dimethoxy-pyrimidine

To an ice-cooled stirred suspension of 2-amino-4,6-dimethoxypyrimidine(1.55 g, 10 mmol) in dichloromethane (50 mL) and potassium carbonate(2.76 g, 20 mmol) in water (20 mL) was added 3,4,4-trifluoro-3-butenoylchloride (3.17 g, 20 mmol). The reaction mixture was stirred in cold for10 min and at r.t. for 15 min. The organic layer was washed with 3N HCl(2×25 mL), saturated sodium bicarbonate (25 mL) and brine, and dried.Evaporation of the solvent gave 0.296 g (10%) of the title compound as awhite solid. m.p. 127°-130° C.

EXAMPLE 7 4- (3,4,4-trifluoro-1-oxo-3-butenyl)amino!-benzenesulfonicacid

To an ice-cooled solution of sulfanilic acid (3.90 g, 20 mmol) andsodium bicarbonate (1.68 g, 20 mol) in water (30 mL) was added3,4,4-trifluoro-3-butenoyl chloride (3.17 g, 20 mol) in 5 mln withstirring. The mixture was stirred in cold for 15 min and at r.t. for onehour. The solution was acidified with 8.0 mL of 25% sulfuric acid withcooling and then extracted with n-butanol (2×60 mL). The organic layerwas washed with brine and concentrated and the residue was trituratedwith ether, filtered and dried to give 4.2 g of a white solid. Theproton NMR spectrum of this material indicated the presence of approx.90% of the desired product and 10% of unreacted sulfanilic acid. Thismaterial was redissolved in 75 mL of n-butanol and washed twice with 6NHCl (30 and 15 mL) and brine. The residue obtained after evaporation ofthe solvent was treated with methanol/ether and filtered. Evaporation ofthe tiltrate gave 0.61 g (10%) of the desired product as a white solid.m.p. >300° C.

EXAMPLE 9 3,4,4-trifluoro-N- (trifluoromethyl)sulfonyl!-3-butenamide

To an ice-cooled solution of trifluoromethanesulfonamide (2.75 g, 18.4mmol) in 7.4 mL of 2.5 N sodium hydroxide was added3,4,4-trifluoro-3-butenoyl chloride (2.93 g, 18.5 mmol) with stirring in2 min. The mixture was stirred in cold for 30 min and the whiteprecipitate formed was filtered, washed with cold water (10 mL) anddried to give 0.82 g (16%) of the desired product as a white solid. m.p.115°-120° C.

EXAMPLE 11 1-(3,4,4-trifluoro-1-oxo-3-butenyl)-1H-1,2,4-triazole

To a solution of 1,2,4-triazole (1.38 g, 20 mmol) in ethyl acetate (100mL) was added 3,4,4-trifluoro-3-butenoyl chloride (1.59 g, 10 mmol) atr.t. with stirring. The mixture was stirred for 30 min and filtered. Theresidue obtained after evaporation of the solvent was redissolved indichloromethane (25 mL) and filtered. Evaporation of the solvent gave1.8 g (94%) of the desired product as a dear oil.

EXAMPLE 13 3,4,4-trifluoro-N-phenyl-3 -butenethioamide

A mixture of 3,4,4-trifluoro-N-phenyl-3-butenamide (1.0 g, 4.65 mmol)and phosphorus pontasulfide (2.07 g, 4.65 mmol) in anhyd. THF (100 mL)was heated at reflux under nitrogen for 1 hour. The reaction mixture wascooled to r.t. and filtered. The tiltrate was concentrated and theresidue was chromategraphed over silica gel (dichloromethane/hexanes,80/20) to give 0.65 g (60%) of the desired compound as a pale yellowsolid. m.p. 65°-67° C.

EXAMPLE 15 3-Butenethioic acid, 3,4,4-trifluoro-, s-2-(trlmethylsilyl)ethyl!ester

To an ice-cooled suspension of 2-(trimethylsilyl)ethanethiol (1.0 g, 7.5mmol) in dichloromethane (35 ml,) and 10% aqueous sodium hydroxide (6.0mL) was added 3,4,4-trifluoro-3-butenoyl chloride (2.38 g, 15 mmol) withstirring. The mixture was stirred in cold for 30 min and the organiclayer was washed with sturated sodium bicarbonate and brine, and dried.The residue obtained after evaporation of the solvent was kugelrohrdistilled at 0.5 mmHg (pot temperature 50°-60° C.) to give 1.1 g (56%)of the title compound as a clear oil.

EXAMPLE 17 Diethyl (2,3,3-trifluoro-2-propenyl)phosphonate

An ice-cooled solution of 2,3,3-trifluoro-2-propen-1-ol (11.2 g, 0.1mole) and two drops of pyridine in dry ether (100 mL) was treated withphosphorus tribromide (9.47 g, 0.035 mole), and the mixture was stirredin cold for one hour and at r.t. for overnight. The solution was washedwith 5% sodium bicarbonate and brine, and dried. The solvent wasdistilled off using a 15 cm vigreaux column to give 14.0 g (80%) of2,3,3-trifluoro-2-propenyl bromide.

A solution of 2,3,3-trifluoro-2-propenyl bromide (5.25 g, 30 mmol) andtriethyl phosphite (4.15 g, 25 mmol) in acetonltrile (15 mL) was heatedat reflux for overnight. The residue obtained after evaporation of thesolvent was chromatographed over silica gel (hexanes/ethylacetate/ethanol, 80/20/1) to give diethyl(1,1,2-trifluro-2-propenyl)phosphonate (0.8 g, 11%) and diethyl(2,3,3-trifluro-2-propenyl)phosphonate (1.0 g, 14%).

EXAMPLE 18 2,3,3-trifluoro-2-proponylphosphonic acid

A solution of di-t-butyl hydroxymethylphosphonate (2.0 g, 8.9 mmol) andtriethylamine (1.27 g, 12.6 mmol) in dichloromethane (15 mL) was treateddropwise with a solution of triflic anhydride (1.8 mL, 10.72 mmol) indichloromethane (5 mL) at -78° C. maintaining the internal temperature<-50° C. The solution was warmed to -30° C. and then recooled to -78° C.and poured onto 100 mL of hexanes and 30 mL of saturated sodiumbicarbonate solution The organic phase was washed with water and brine,and dried. Evaporation of the solvent gave 3.18 g (100%) of(di-t-butylphosphinyl)-methyl trifluoromethylsulfonate as a light brownoil.

An ice-cooled solution of trifluoroethylenylzinc bromide (11.2 mmol) inanhyd. DMF (13 mL) was first stirred with copper(I)bromide (0.8 g, 5.57mmol) for 30 min and allowed to reach r.t. To this solution was added(di-t-butylphosphinyl)methyl trifluoromethylsulfonate (2.5 g, 7.0 mmol)and stirred at r.t. for 4 hours and at 40°-45° C. for 30 min. Thereaction mixture was then poured onto 30 mL of saturated ammoninmchloride and 100 mL of ether. The aqueous layer was extracted once againwith 50 mL of ether and the combined ether extracts were washed withsaturated sodium bicabonate, water and brine, and dried. The residue(0.9 g) obtained after evaporation of the solvent was chromatographedover silica gel (25/75, ethyl acetate/-hexanes) to give 0.5 g ofdi-t-butyl 2,3,3-trifluoro-2-propenylphosphonate as a yellow oil.

The above di-t-butylphosphonate (0.5 g) was dissolved in 3 mL ofmethanol and treated with 0.5 mL, of 3N HCl and allowed to stand at r.t.for 30 min. The solution was concentrated and the residue wasredissolved in 10 mL of water and washed with 10 mL of ether.Evaporation of the aqueous layer gave 0.14 g of2,3,3-trifluoro-2-propenylphosphonic acid as a yellow oil.

EXAMPLE 19

Sodium 2,3,3-trifluoro-2-proponylphenylphosphinate An ice-cooledsolution of trifluoroethylenyI zinc bromide (11.2 mmol) in anhyd. DMF(13 mL) was first stirred with copper(I)bromide (0.8 g, 5.57 mmol) for30 min and allowed to reach r.t. To this solution was added(t-butoxyphenylphosphinyl)methyl trifluoromethane sulfonate (2.0 g, 5.55mmol) and stirred at r.t. for 4 hours and at 40°-45° C. for 30 min. Thereaction mixture was then poured onto 40 mL of saturated ammoniumchloride and 5 mL of 3N HCl and extracted with ethyl acetate twice (75and 50 mL). The combined ethyl acetate extract was washed with water(2×50 mL), and extracted with 5% sodium bicarbonate (2×15 mL). Thesodium bicarbonate extract was acidified with conc. HCl with cooling andextracted with ethyl acetate (3×40 mL). The combined ethyl acetateextracts were washed with brine and dried. Evaporation of the solventgave 0.62 g of a brown viscous material which was dissolved in 2.5 mL ofwater containing 0.22 g of sodium bicarbonate and purified by HPLC (C-18reverse phase, water/acetonitrile) to give 0.254 g of the title compoundas a white solid. m.p. 278°-279° C.

EXAMPLE 20

3,4,4-trifluoro-1-(2-methylphenyl )-3-buten-1-one

To a solution of 3,4,4-trifluoro-3-butenoyl chloride (3.75 g, 23.65mmol) in anhyd. ether (100 mL) was treated with copper(I)iodide (2.28 g,12 mmol) followed by 24 mL of 1.0M solution of benzylmagnesinm chloridein ether dropwise at -78° C. with stirring under nitrogen. The reactionmixture was stirred at -78° C. for 10 min and allowed to reach to r.t.and filtered. The flitrate was successively washed with 2N HCl, 5%sodium bicarbonate and brine, and dried. The residue, a mixture ofseveral products, obtained after evaporation of the solvent waschromotographed over silica gel (20% hexanes in dichloromethane) and themajor product (least polar) was isolated and further purified bykugelrohr distillation, b.p. 130°-140° C. (pot temperature)-/12 mmHg.Proton and fluorine NMR spectra of this material was found to correspondto the title compound.

Examples 2 and 6 are likewise prepared in a manner analogous to Example5 using the appropriate starting materials.

Example 12 is prepared in a manner analogous to Example 11 using theappropriate starting material.

Examples 3, 4, 8, 10, 14, and 16 are prepared in a manner analogous toExample 15 using the appropriate starting materials.

The following table describes the chemical structures of the examples.

    __________________________________________________________________________    Example                                                                       Number                                                                             Name                Structure                                            __________________________________________________________________________     1   PHOSPHONIC ACID,   (3,4,4-TRIFLUORO-1-OXO-3- BUTENYL)AMINO!METHYL!-,          ISODIUM SALT, DIHYDRATE  MP: 190.0-200.0                                                           ##STR8##                                             2   3-BUTENAMIDE, N-(CYANOMETHYL)-3,4,4- TRIFLUORO- MP:                                                ##STR9##                                             3   3-BUTENAMIDE,  3,4,4-TRIFLUORO-N-METHOXY- MP: 46.0-49.0                                            ##STR10##                                            4   3-BUTENOIC ACID, 3,4,4-TRIFLUORO-,  2-(AMINOCARBONYL)HYDRAZIDE  MP:           132.0-138.0                                                                                        ##STR11##                                            5   3-BUTENAMIDE,  N-(4,6-DIMETHOXY-2-PYRIMIDINYL)- 3,4-4-TRIFLUORO- MP:          127.0-130.0                                                                                        ##STR12##                                            6   3-BUTENAMIDE, 3,4,4-TRIFLUORO-N- (PHENYLMETHYL)-N-  (TRIMETHYLSILYL)M         ETHYL!- oil                                                                                        ##STR13##                                            7   BENZENESULFONIC ACID, 4- (3,4,4-TRIFLUORO-1-OXO-3- BUTENYL)AMINO!-            MP: 300.0                                                                                          ##STR14##                                            8   3-BUTENAMIDE, 3,4,4-TRIFLUORO-N- (METHYLSULFONYL)- MP:                                             ##STR15##                                            9   3-BUTENAMIDE, 3,4,4-TRIFLUORO-,N-  (TRIFLUOROMETHYL) SULFONYL!- MP:           115.0-120.0                                                                                        ##STR16##                                           10   METHANESULFONIC ACID,  (3,4,4-TRIFLUORO-1-OXO-3- BUTENYL)AMINO!- MP:          264.0-267.0                                                                                        ##STR17##                                           11   1H-1,2,4-THIAZOLE, 1-(3,4,4-TRIFLUORO-1-OXO-3- BUTENYL)- oil                                       ##STR18##                                           12   1H-PYRAZOLE, 1-(3,4,4-TRIFLUORO-1-OXO-3- BUTENYL)- oil                                             ##STR19##                                           13   3-BUTENETHIOAMIDE, 3,4,4-TRIFLUORO-N-PHENYL MP: 65.0-67.0                                          ##STR20##                                           14   3-BUTENOIC ACID, 3,4,4-TRIFLUORO-, 3-(TRIMETHYLSILYL)PROPYL ESTER             oil                                                                                                ##STR21##                                           15   3-BUTENETHIOIC ACID, 3,4,4-TRIFLUORO-, S- 2-(TRIMETHYLSILYL)ETHYL!            ESTER oil                                                                                          ##STR22##                                           16   3-BUTENETHIOIC ACID, 3,4,4-TRIFLUORO-, S-2-PYRIMIDINYL ESTER                                       ##STR23##                                           17   PHOSPHONIC ACID, (2,3,3-TRIFLUORO-2-PROPENYL)-, DIETHYL ESTER                                      ##STR24##                                           18   PHOSPHONIC ACID, (2,3,3-TRIFLUORO-2-PROPENYL)- oil                                                 ##STR25##                                           19   PHOSPHONIC ACID, PHENYL(2,3,3-TRIFLUORO-2- PROPENYL)-,SODIUM SALT             MP: 278.0-279.0                                                                                    ##STR26##                                           20   3-BUTEN-1-ONE, 3,4,4-TRIFLUORO-1-(2- METHYLPHENYL)- oil                                            ##STR27##                                           __________________________________________________________________________

Compounds of formula I are prepared by methods analogous to thosedescribed herein or known in the literature using starting materialsdescribed herein or known in literature or which can be prepared bymethods analogous to those in the literature.

COMPOSITIONS

In normal use, the compounds usually will not be employed free fromadmixture or dilution, but ordinarily will be used in a suitableformulated composition compatible with the method of application andcomprising an effective amount of the compound. The compounds of thisinvention, like most agricultural agents, may be blended withagriculturally acceptable surface-active agents and carriers normallyemployed for facilitating the dispersion of active ingredients,recognizing the accepted fact that the formulation and mode ofapplication may affect the activity of the material.

The present compounds may be applied to the above ground portion ofplants or they may applied to the soil. The present compounds may beapplied, for example, as sprays, dusts, seed treatments or granules, tothe area where post control is desired, the type of application varyingwith the post and the environment. Thus, the compounds of this inventionmy be formulated as granules of large particle size, as powdery dusts,as wettable powders, as emulsifiable concentrates, as solution, and thelike.

Granules may comprise porous or nonporous particles, such as attapulgiteclay or sand, for example, which serve as carriers for the presentcompounds. The granule particles are relatively large, a diameter ofabout 400-2500 microns typically. The particles are either impregnatedwith the compound of the invention from solution or coated with thecompound, adhesive sometimes being employed. Granules generally contain0.05-10%, preferably 0.5-5%, active ingredient.

Dusts are admixtures of the compounds, with finely divided solids suchas talc, attapulgite clay, kieselguhr, pyrophyllite, chalk, diatomaceousearths, calcium phosphates, calcium and magnesinm carbonates, sulfur,flours, and other organic and inorganic solids which act as carriers forthe compound. These finely divided solids have an avenge particle sizeof less than about 50 microns. A typical dust formulation contains 1part of compound and 99 parts of talc.

The compounds of the present invention may be made into liquidconcentrates by dissolution or emulsification in suitable liquids andinto solid concentrates by admixture with talc, clays, and other knownsolid carriers used in the agricultural chemical art. The concentratesare compositions containing about 5-50% active compound and 95-50% inertmaterial, which includes surface-active dispersing, emulsifying, andwetting agents, but even higher concentrations of active ingredient maybe employed experimentally. The concentrates are diluted with water orother liquids for practical application as sprays, or with additionalsolid carrier for use as dusts.

A typical 50% wettable powder formulation would consist of 50.0% (wt/wt)of active ingredient, 22.0% attapulgite diluent, 22.0% of kaolindiluent, and 6.0% sodium salts of sulfonated Kraft lignin emulsifier.

Typical carriers for solid concentrates (also called wettable powders)include fuller's earth, clays, silicas, and other highly absorbent,readily wetted inorganic diluents. A suitable solid concentrateformulation may contain 1.5 parts each of sodium lignosulfonate andsodium lauryl sulfate as wetting agents, 25 parts of active compound and72 parts of attapuigite clay.

Manufacturing concentrates are useful for shipping low melting productsof this invention. Such concentrates are prepared by melting the lowmelting solid products together with one percent or more of a solvent toproduce a concentrate which does not solidify on cooling to the freezingpoint of the pure product or below.

Useful liquid concentrates include the emulsifiable concentrates, whichare homogeneous liquid or paste compositions readily dispersed in wateror other liquid carriers. They may consist entirely of the activecompound with a liquid or solid emulsifying agent, or they may alsocontain a liquid carrier such as xylene, heavy aromatic naphthas,isophorone and other relatively non-volatile organic solvents. Forapplication, these concentrates are dispersed in water or other liquidcarders and normally applied as sprays to areas to be treated.

A typical 50 gram per liter emulsifiable concentrate formulation wouldconsist of 5.9% (wt/wt) of a compound of the invention; as emulsifiers;1.80% of a blend of the calcium salt of dodecylbenzene sulfonate andnonionic 6-molar ethylene oxide condensation product of nonylphenol,2.70% of a blend of the calcinm salt of dodecylbenzene sulfonate and anonionic 30-molar ethylene oxide condensation product of nonylphenol,1.50% of a nonionic paste of polyalkylene glycol ether, and 88.10%refined xylene solvent.

Typical surface-active wetting, dispersing, and emulsifying agents usedin agricultural formulations include, for example, the alkyl andalkylaryl sulfonates and sulfates and their sodium salts; alkylamidesulfonates, including fatty methyl taurides; alkylaryl pelyetheralcohols, sulfated higher alcohols, pelyvinyl alcohols; polyethyleneoxides; sulfonated animal and vegetable oils; sulfonated petroleum oils;fatty acid esters of polyhydric alcohols and the ethylene oxide additionproducts of such esters; and the addition products of long-chainmercaptans and ethylene oxide. The surface active agent normallycomprises about 1-15% by weight of the active ingredient.

Other usefid formulations include simple solutions of the activeingredient in a solvent in which it is completely soluble at the desiredconcentration, such as water, acetone, or other organic solvents. Thepreferred formulation for foliar application is on aqueous solution,more preferably containing glycerin and a surfactant, such as Tween®20,and most preferably 1% glycerin and 0.1% Tween®20.

The compositions may be formulated and applied with suitable pesticidalactive ingredients, including insecticides, acaricides, fungicides,plant regulators, herbicides, fertilizers, etc.

METHODS OF USE BIOLOGICAL EVALUATION METHOD

Compounds of the present invention, prepared as described above, weretested for effectiveness in controlling root knot nematodes (Meloidogyneincognita) on tomato roots when applied to foliage of young plants.

Tomato plants, cv `Rutgers`, were grown one per pot in six cm squareplastic pots contining a mixture of equal parts fine sand, coarse sand,silt loam soil, and commercial potting medium. A 10,000 ppm stocksolution of each test compound was prepared in either water or acetone.Samples were then diluted with additional water to give final testconcentrations of 500 and 100 ppm. Tween®20 was added for a finalconcentration of 0.5% v/v in all test samples.

When the tomato plants were 18-21 days old the test solutions weresprayed onto the leaves and stems. Each rate of each test compound wasapplied to three tomato plants using four ml of spray solution perplant. One day after spraying the plants were inoculated with matureroot knot nematode eggs containing J1 larvae, with 8,000 eggs per plantapplied in 5 ml of water on soil at the stem base. Plants then wereincubated in a growth chamber at 27° C. with all replicate potsrandomized throughout the chamber. During the two weeks immediatelyfollowing application of the test compounds all plants receivedsub-irrigation and the foliage was kept dry.

After three weeks incubation the plant roots were washed and nematodedisease severity was assessed. Each root system was rated individuallyand a visual estimate of the percent of the root system afflicted withnematode galling was determined. Values of 0, 1, 5, 10, 20, 30, 40, 50,60, 70, 80, or 100 percent galled roots were assigned to each plant.Non-treated plants generally received root ratings of 60% disease orgreater. For each treatment (compound & rate) a standard deviation wascalculated for the mean of the three replicate plants. Percent diseasecontrol relative to non-treated plants also was calculated.

                  TABLE 1                                                         ______________________________________                                        Mean percent root disease (galled), the standard deviation of                 that mean (std dev), and percent control of                                   root disease relative to non-treated plants.                                  Example   ppm    % disease   std dev                                                                             % control                                  ______________________________________                                         1        500    80          0.00   0*                                         1        100    87          4.71  -8                                          2        500    67          11.55 17                                          2        100    73          11.55  8                                          3        500    70          20.00 20                                          3        100    77          11.55 12                                          4        500    73          5.77   8                                          4        100    80          0.00   0*                                         5        500    30          20.00 66                                          5        100    90          0.00  -3                                          6        500    87          5.77   0*                                         6        100    85          7.07   2                                          7        500    17          5.77  69                                          7        100    23          5.77  56                                          8        500     5          0.00  94                                          8        100    80          0.00   0*                                         9        500     5          0.00  94                                          9        100    80          0.00   0*                                        10        500    27          11.55 50                                         10        100    20          10.00 62                                         11        500     7          2.89  92                                         11        100    80          0.00   0*                                        12        500    43          15.28 46                                         12        100    80          0.00   0*                                        13        500    27          15.28 50                                         13        100    40          10.00 25                                         14        500    80          0.00   8                                         14        100    83          5.77   4                                         15        500    90          0.00  -3                                         15        100    85          7.07   2                                         16        500    50          10.00 38                                         16        100    80          0.00   0*                                        17        500    27          15.28 50                                         17        100    30          10.00 44                                         18        500    73          5.77   0*                                        18        100    77          5.77  -5                                         19        500    73          5.77   0*                                        19        100    73          5.77   0*                                        20        500    47          11.55 12                                         20        100    53          5.77   0*                                        ______________________________________                                         * = no biological activity at the rate tested                            

What is claimed is:
 1. A compound having the structure: ##STR28##wherein Q is (C═W)--R₂ ;wherein W is 0 or S; R₂ is (a) --OR₅₀, --SR₅₀,or --NR₅₀ R₆₀ wherein R₆₀ is hydrogen or R₅₀ ; and wherein R₅₀ is(i) aheterocyclic group, substituted with at least one group selected from aradical of sulfonic acid, phosphonic acid, phosphinic acid, theiresters, amides and thio esters; cyano, or trimethylsilyl and optionallyfurther substituted with one of hydroxy, alkoxy, halo, nitro, amino,thiol, alkylthio, carboxyl, alkoxycarbonyl, or phenyl; ii R₅₀ and R₆₀taken together with the N-atom to which they are attached is a cyclicgroup selected from a radical of morpholine, piperidine, piperazine, orpyrrolidine, substituted with at least one group selected from a radicalof sulfonic acid, phosphonic acid, phosphinic acid, their esters, amidesand thio esters; cyano, or tfimethylsilyl and optionally furthersubstituted with one of hydroxy, alkoxy, halo, nitro, amino, thio,alkylthio, carboxyl, alkoxycarbonyl, or phenyl; iii R₅₀ and R₆₀ takentogether with the N-atom to which they are attached are pyrazole,imidazole or triazole, optionally substituted with at least one groupselected from a radical of sulfonic acid, phosphonic acid, phosphinicacid, carboxylic acid, their esters, amides and thio esters; cyano, ortrimethylsilyl, hydroxy, alkoxy, halo, nitro, amino, thio, alkylthio, orphenyl; or (b) A heterocyclic group optionally substituted with aradical of sulfonic acid, phosphonic acid, phosphinic acid, carboxylicacid, their esters, amides and thioesters, cyano, trimethylsilyl,hydroxy, alkoxy, halo, nitro, amino, thiol, alkylthio, or phenyl; withthe proviso that when W is S and the heterocyclic group contains a Natom, then the point of attachment to the heterocyclic group must bethrough a N atom and with the further proviso that when W is O and R₂ is(b), the heterocyclic group can not be morpholine, piperidine,piperazine or pyrrolidine;or any agronomically acceptable salt thereof.2. A compound of claim 1 wherein W is O.
 3. A compound of claim 1wherein R₂ is OR₅₀, --SR₅₀, or --NR₅₀ R₆₀.
 4. A compound of claim 3wherein R₂ is --NR₅₀ R₆₀.
 5. A compound of claim 4 wherein one of R₆₀ isheterocyclic.
 6. A compound of claim 5 which is2-(3,4,4-trifiuore-1-oxo-3- butenyl)amino-4,6-dimethoxy-pyrimidine.
 7. Acompound of claim 1 which is1-(3,4,4-trifluoro-1-oxo-3-butenyl)-1H-1,2,4-triazole.
 8. A compositionfor controlling nematode infestation of a plant comprising an effectivemount of a compound of claim 1 in an agronomically acceptable carrier.9. A method of systemically controlling nematode, insect or acarldinfestation of a plant, comprising applying to a plant locus aneffective amount of a compound of claim 1.